Adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in boys and girls (≥1 year postmenarchal) 10–16 years of age who, despite an adequate trial of dietary management, have a serum LDL-cholesterol concentration of ≥190 mg/dL or a serum LDL-cholesterol concentration of ≥160 mg/dL and either a family history of premature cardiovascular disease or ≥2 other cardiovascular risk factors.172

Reduction of total and LDL-cholesterol concentrations in patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus† (diabetic dyslipidemia),54 renal insufficiency†,63 cardiac† or renal transplantation†,2021222127555764 or nephrotic syndrome† (nephrotic hyperlipidemia).2465

Fluvastatin Sodium Dosage and Administration

General

Patients should be placed on a standard lipid-lowering diet before initiation of fluvastatin therapy and should remain on this diet during treatment with the drug.160

Dosage

Pediatric Patients

Dyslipidemias

Oral

Adjust dosage at 6-week intervals until the desired effect on lipoprotein concentrations is observed or a daily dosage of 80 mg (administered as 40 mg twice daily as conventional capsules or 80 mg once daily as extended-release tablets) is reached.172

Adults

Prevention of Cardiovascular Events or Management of Dyslipidemias

Oral

Patients who require reductions in LDL-cholesterol concentrations of <25%: Initially, 20 mg once daily in the evening.1

Patients who require reductions of >25% in LDL-cholesterol concentrations or patients with primary hypercholesterolemia or mixed dyslipidemia: Initially, 40 mg (as conventional capsules) once daily in the evening, 80 mg (as extended-release tablets) once daily at any time of day, or 40 mg (as conventional capsules) twice daily.172

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.1

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

Administer to women of childbearing age only when they are highly unlikely to conceive and have been informed of the potential hazards.1 If the patient becomes pregnant while taking the drug, discontinue therapy and apprise the patient of the potential hazard to the fetus.1

Musculoskeletal Effects

Myopathy (manifested as muscle pain, tenderness, or weakness and serum CK [CPK] concentration increases >10 times the ULN) has been reported.1

Rhabdomyolysis (characterized by muscle pain or weakness with marked increases [>10 times the ULN] in serum CK concentrations and increases in Scr [usually accompanied by brown urine and urinary myoglobinuria]) with acute renal failure secondary to myoglobinuria has been reported.172

Obtain serum CK concentrations and compare with baseline concentrations in patients presenting with musculoskeletal symptoms suggestive of myopathy; because hypothyroidism may be a predisposing factor, TSH concentrations also should be obtained in such patients.

Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked CK elevation.72 Discontinue therapy if serum CK concentrations become markedly elevated or if myopathy is diagnosed or suspected.1

Monitor patients weekly if myalgia (muscle pain, tenderness) is present with either no CK elevation or a moderate elevation (3–10 times the ULN) until manifestations improve; discontinue if manifestations worsen.

Dosage reduction or temporary discontinuance may be prudent in patients with muscle discomfort and/or weakness in the presence of progressive elevation of CK concentrations on serial measurements.

Hepatic Effects

Increases in serum aminotransferase (AST, ALT) concentrations reported.1 Generally transient and resolve or improve with continued therapy or after temporary interruption in therapy.72

Persistent aminotransferase elevations (>3 times the ULN on 2 consecutive weekly measurements) are more common at higher dosages (40 or 80 mg daily).72 Most cases occurred within 12 weeks of therapy.72

Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage201 ).72 Although manufacturer previously recommended more frequent monitoring, FDA concluded that serious statin-related liver injury is rare and unpredictable, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.200

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt fluvastatin therapy.72 If an alternate etiology is not found, do not restart fluvastatin.72

Endogenous Steroid Production

Fluvastatin had no effect on nonstimulated cortisol concentrations, adrenal response to corticotropin (adrenocorticotropic hormone, ACTH) stimulation, or thyroid metabolism.72 Small declines in total serum testosterone concentrations reported, but no commensurate elevation in LH concentrations, and no effect on FSH concentrations in men.72 Data insufficient to determine effect on female sex hormones.72

Caution advised if a statin or another antilipemic agent is used concomitantly with drugs that may decrease concentrations or activity of endogenous steroid hormones (e.g. ketoconazole, spironolactone, cimetidine).72

Cognitive Impairment

Generally nonserious and reversible, with variable times to symptom onset (1 day to years) and resolution (median of 3 weeks following discontinuance of therapy).72200 Not associated with fixed or progressive dementia (e.g., Alzheimer’s disease) or clinically important cognitive decline.200 Not associated with any specific statin, patient's age, statin dosage, or concomitant drug therapy.200

FDA states that cardiovascular benefits of statins outweigh the small increased risk of cognitive impairment.200

Role as Adjunct Therapy

Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.1

Specific Populations

Pregnancy

Category X.1 (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Distributed into milk in animals.72 Use is contraindicated in nursing women; women who require fluvastatin therapy should not breast-feed their infants.72

Pediatric Use

Safety and efficacy not established in children <9 years of age or in premenarchal girls.172 (See Advice to Patients.)

Geriatric Use

Fluvastatin exposures not substantially different between patients ≥65 years of age and younger adults.72

Use with caution, since age ≥65 years is a predisposing factor for myopathy.72

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.1

Onset

A therapeutic response usually is apparent within 2 weeks after initiating therapy, with a maximal response occurring within 4 weeks.1

Food

Peak plasma concentration decreased and time to peak plasma concentrations increased following administration of fluvastatin conventional capsules with the evening meal; however, no substantial differences in lipid-lowering effects following administration with food.172

Bioavailability increased and absorption delayed following administration of extended-release tablets with a high-fat meal; however, peak plasma concentrations achieved with the extended-release tablets following a high-fat meal are much less than those achieved with a single or twice-daily dose of 40 mg.1

Importance of informing patients about risks, especially rhabdomyolysis, associated with statins alone or combined with other drugs.1 Importance of patients promptly reporting muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.1

Risk of increased glucose concentrations and development of type 2 diabetes.72200 May need to monitor glucose concentrations following initiation of statin therapy.201

Importance of advising women and adolescent girls to avoid pregnancy (i.e., using effective contraceptive methods) during therapy; if the patient becomes pregnant, importance of immediately discontinuing fluvastatin and contacting a clinician.172

Importance of avoiding breast-feeding during therapy.72 If the patient has a lipid disorder and is breast-feeding, importance of contacting a clinician to discuss other antilipemic treatment options.72

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fluvastatin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg (of fluvastatin)*

Fluvastatin Sodium Capsules

Lescol

Novartis

40 mg (of fluvastatin)*

Fluvastatin Sodium Capsules

Lescol

Novartis

Tablets, extended-release

80 mg (of fluvastatin)

Lescol XL

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

29. American Heart Association Committee to Design a Dietary Treatment of Hyperlipoproteinemia. Recommendations for treatment of hyperlipidemia in adults: a joint statement of the Nutrition Committee and the Council on Arteriosclerosis. Circulation. 1984; 69:1065-90A. [PubMed 6713610]

68. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-23.

69. Expert Panel on Detection, Evaluation, and Treatment of high Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of high Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285:2486-97. [IDIS 464555] [PubMed 11368702]